Research Review

Corneal Infiltrates: Managing Risks With Soft Lens Wear

Research Review

Corneal Infiltrates: Managing Risks With Soft Lens Wear

By Loretta B. Szczotka-Flynn, OD, PhD, FAAO, and Robin Chalmers, OD, FAAO

Corneal infiltrates can occur in contact lens wearers and nonwearers alike and are a result of a stimulus that directs infiltration of leukocytes into the cornea (Josephson,1979). Recently, clinical reports have purported an increased incidence of corneal infiltrates with silicone hydrogel lenses and multipurpose care solutions (Hine, 2008; Kislan, 2011;Sacco, 2011). This review summarizes the incidence of and risk factors for corneal infiltrates across various soft lens types and summarizes what is known about risks for corneal infiltrates with silicone hydrogel lenses and multipurpose care solutions in the peer-reviewed literature.

Symptomatic Infiltrate Rates

The rate of corneal infiltrates documented in any given study is significantly affected by definition and frequency of examination. The most clinically relevant rates probably come from clinical studies that report symptomatic corneal infiltrates, since those encompass patients who present for care related to corneal infiltrates. During 30-night extended wear with silicone hydrogels, the incidence of symptomatic corneal infiltrates (or >= Grade 2) has been documented at 2.5 to ~6 percent per year (Chalmers, 2007; FDA Summary of Safety and Effectiveness Data [balafilcon A], 2001; FDA Summary of Safety and Effectiveness Data [lotrafilcon A], 2001). A meta-analysis of 23 extended-wear studies from the 1990s until 2006 reported the annual rate of symptomatic and asymptomatic corneal infiltrate events to be 14.4 percent for silicone hydrogels and 7.7 percent for hydrogel materials (Szczotka-Flynn, 2007).

Risk factors for corneal infiltrates with daily wear of silicone hydrogels have been established, but the incidence is not known. A university-based study team assessed corneal infiltrates in a series of 3-month, nonrandomized, prospective clinical trials with 558 individuals wearing a variety of silicone hydrogel lenses for daily wear and using modern lens care products (Carnt et al, 2009). In these trials, the rate of symptomatic corneal infiltrates was ~20 percent when annualized to 1 year but varied widely by care solution brand and lens material. Subjects in university studies are sometimes examined frequently, which may increase the observed incidence of corneal filtrates (Chalmers, 2007). In two large, multicenter, retrospective chart reviews, the incidence of corneal infiltrates across multiple lens types for patients presenting for eye care in optometry school clinics was just over 3 percent per year in studies that reviewed records from 6,117 patient-years of contact lens wear (Chalmers et al, 2011; Chalmers et al, 2011). These rates may more closely align with what practitioners see in practice.

Risk Factors

Risk factors are estimates of how much a certain factor increases or decreases a person's chance of developing a specific disease. In health research, the best approach is to consider the multivariate risk factors, because they account for the influence of many factors that each person may carry that may influence (or confound) one another. For example, corneal infiltrate risk may be higher for patients wearing silicone hydrogel contact lenses because they are more likely to sleep in these lenses,even if they have been prescribed for daily wear. A multivariate analysis will control for overnight wear and material separately and measure the influence of each factor. We present multivariate factors here.

Studies of risk factors for corneal infiltrates have been consistent, and they include factors brought by the patient, the lens wear modality, the lens material and the care products. Significant factors related to patients include male gender (du Toit, 2002), smoking (Szczotka-Flynn et al, 2010; McNally et al, 2003), absolute refractive error ≥5.00D (Chalmers et al, 2007), history of previous complications (McNally et al, 2003) and young age (Chalmers et al, 2007; Chalmers et al, 2011; Chalmers et al, 2011; McNally et al, 2003; Chalmers et al, 2010).

Substantial lens bacterial bioburden increases the risk for corneal infiltrates during silicone hydrogel lens extended wear more than eight-fold (Szczotka-Flynn et al, 2010), and similar results have been found with low-Dk HEMA-based materials (Wilcox et al, 2011). Bioburden is responsible for more than 70 percent of the total risk of corneal infiltrates in silicone hydrogel extended wear (Szczotka-Flynn et al, 2010).

Extended wear increases the risk for corneal infiltrates 2.5-fold to eight-fold across various soft lens types (Chalmers, et al 2011; Efron et al, 2005; Radford et al, 2009). Although corneal staining is common during extended wear with silicone hydrogel lenses, it is not associated with the development of a corneal infiltrate (Szczotka-Flynn et al, 2010). One study claimed daily disposables did not lower corneal infiltrate risk (Radford et al, 2009), but more recent studies find either no difference (Chalmers et al, 2010) or up to a 12.5-fold lower risk of corneal infiltrates for daily disposables compared with reusable lenses (Chalmers et al, 2011).

Products associated with increased risk include multipurpose disinfection systems (about a three-fold increased risk compared to peroxide systems) (Chalmers et al, 2011) and silicone hydrogel lenses. In at least four studies, silicone hydrogel materials have been associated with about a two-fold greater risk for corneal infiltrates compared with hydrogel materials, regardless of overnight wear (Szczotka-Flynn, 2007; Chalmers et al, 2011; Chalmers et al, 2011; Radford et al, 2009). This increased rate of corneal infiltrates in silicone hydrogel wearers is perplexing, as we effectively prescribe these lenses to avoid the hypoxic complications we have observed in the past.

The previously mentioned case series and repeated lens-solution trials reported on patients with corneal infiltrates that were believed to be associated with an interaction between Opti-Free Replenish (Alcon Laboratories Inc.) and silicone hydrogel lenses. That finding did not hold up in a recent retrospective, multicenter, case-control study that had the capability (power) to detect whether specific products or combinations of lenses and lens care products had at least a 1.8-fold increased risk for corneal infiltrates (Chalmers et al, 2011). A case-control study compares product use among patients who develop disease and patients from the same practice and time period who remained disease free and, thus, accounts for the market share of a product that can confound the findings seen in a case series. This study found that more than 45 lens-solution combinations were used by 166 patients who presented with corneal infiltrates related to contact lens wear and that the risk was not limited to a very few products. No significant increase in risk was seen with any one lens care product when other factors were taken into account (multivariate analysis). There are perhaps some regional effects driving the corneal infiltrate cases in the private practice case series.

Implications of the Evidence

Although the increased rate of corneal infiltrates with silicone hydrogels is apparent in the literature, the benefits of these lenses may outweigh this risk, at least for many patients. The higher incidence of corneal infiltrates found in prospective studies frequently includes asymptomatic events, while the benefits include reduced hypoxic complications and longer wearing times for the same level of microbial keratitis risk (Schein et al, 2005). Regarding care solution interaction as a risk factor, it is important to evaluate study design when interpreting results.

The most recent literature suggests that no single lens brand or lens care product is associated with a significant increase in risk that even begins to approach the risk associated with extended wear (2.5-fold to eight-fold), use of reusable lenses compared to daily disposable (12.5 times higher), smoking (four-fold) or having a contaminated lens during extended wear (greater than eightfold). Clinicians should use such evidence-based research to customize a treatment plan and guide patients into the best lens for that person. CLS

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Dr. Szczotka-Flynn is a professor at the Case Western Reserve University Department of Ophthalmology & Visual Sciences and director of the Contact Lens Service at University Hospitals Case Medical Center. She has received research funding from Alcon, CooperVision and Vistakon. Dr. Chalmers is an independent clinical trial consultant and an adjunct professor at Indiana University School of Optometry. She is a consultant or advisor to Alcon and Vistakon and an advisor to Bausch + Lomb